As he lay dying: FDA and Huntington’s disease families meet to ponder potential treatments

On Tuesday, September 22, when the U.S. Food and Drug Administration (FDA) focuses on Huntington’s disease drug development at a meeting with affected individuals and advocates, HD families must drive home the sorrowful truth: people are dying because of the lack of effective treatments.

About two weeks ago, shortly after pouring out my heart about my family’s HD struggles on the FDA’s pre-meeting questionnaire, I received a message from the mother of 18-year-old Terry Leach of San Diego: “It’s Terry’s final days if you wanted to say good-bye.”

A couple days later, on Labor Day, I visited Terry, who suffers from juvenile HD, in his bedroom. As Terry slept, his mother Angela and I looked on. Next to us a home healthcare worker prepared a can of liquid food to be administered via a feeding tube attached to Terry’s abdomen. Hospice workers are also helping.

“He grew a lot,” I said to Angela, amazed at how, despite the particularly cruel toll of juvenile HD, his body had strived to develop. It had been more than a year since I had last seen Terry.

“Yes, he did,” Angela said.

I noticed Terry’s beard and his healthy head of somewhat wiry, dark brown hair.

“You have a very handsome son,” I continued.

“Thank you,” Angela said.

Terry Leach resting at home (family photo)

Unspeakable pain

As Angela nervously shifted her balance from foot to foot, I sensed that she continued to carry the unspeakable burden that comes with juvenile HD: Terry’s first symptoms as an infant, his need for a full-time aide in school after losing his ability to walk and talk, the insertion of the feeding tube in 2010, Botox injections into his arms and legs in recent years to relieve pain, and leg and foot operations, among other procedures and hospitalizations.

Although Terry still attended school last academic year and also the summer session, he has declined considerably in the last few months, Angela said.

The night before my visit, he vomited after receiving liquid food through his tube. On the day I visited, the aide would give him only one can instead of the usual two, noting that his body would not accept anything more than that very small amount.

I asked Angela if I could touch Terry.

“Sure,” she said softly.

I ran my hand along the top of his hair. I remembered Angela and her family’s steadfastness in caring for Terry. I also recalled fondly our collaboration in the cause, starting with an article I wrote about them in 2009. In 2012, Terry emerged as “SuperTerry” in an artist’s comic-book like rendition as a hero defeating HD. In 2014, our families participated in the 2014 Team Hope Walk of the San Diego Chapter of the Huntington’s Disease Society of America.

SuperTerry in San Diego artist Lee Ellingson's rendition (above) and with Gene Veritas (aka Kenneth P. Serbin) at the 2014 Team Hope Walk (below, photo by Misty Oto)

Seeking feedback from the community

As Terry lies dying, the September 22 FDA event, a public meeting on “patient-focused drug development,” will seek feedback from affected individuals and others in the HD community.

The meeting will occur from 9 a.m.-12:30 p.m. at the FDA’s White Oak Campus in Silver Spring, MD. Pre-registration for attending the meeting and viewing via webcast is closed, but the FDA will make available a video of the proceedings shortly thereafter.

The meeting stems from the reauthorization of the Prescription Drug User Fee Act in 2012, in which Congress required the FDA to more systematically solicit input from patient communities with regard to drug development. The FDA hopes this will help its review process.

Huntington’s disease became one of just 20 diseases selected by the FDA for a patient-focused meeting through the end of 2015.

‘Nothing for neurological disorders’

Responding to the preparatory questionnaire, I revealed my situation as a carrier of the HD genetic defect and my mother’s decline and death from HD in 2006.

“I fear that I will become like my mother,” I wrote. “She had mild chorea [involuntary movements associated with HD]. I would not mind having chorea as long as I can continue to be myself, work, and not become a burden on my wife and daughter. My mother became a shadow of herself. I have great anxiety about losing my personality and ability to work as a college professor and writer.”

Like others, I would like to see a treatment that prevented symptoms, I added.

“If I get symptoms, then I would like a medication that allows me to manage the disease just as other diseases such as diabetes are managed without affecting a person’s livelihood, family life, or activities in general,” I continued. “There are lots of advances in cancer treatments, for instance, but really nothing in the field of neurological disorders that prevents, halts, or reverses the condition.”

I uploaded my response to the FDA’s public docket regarding the meeting. Anybody can comment at that link through November 23, 2015.

Speeding up clinical trials

At the meeting, I also plan to urge FDA officials to allow researchers and clinical trial administrators to use new technologies to measure the effect of medicines.

All clinical trials of new drugs taking place in the U.S. must receive the approval of the FDA, considered to have the world’s most rigorous standards. Although the drug industry executives I have met recognize the importance of that rigor in assuring the manufacture of safe and effective drugs, they sometimes have also expressed the need for the FDA to be more flexible and allow for faster clinical trials.

Generally, the FDA still does not accept techniques such as brain scans. HD researchers and other scientists are vigorously searching for biomarkers – signs of disease and drug effectiveness – in the blood, cerebrospinal fluid, and other materials taken from the body that can be measured using the scans and other new techniques.

Instead of waiting for a doctor’s clinical observation of an improvement, these techniques could potentially allow faster and earlier reading of a drug’s effectiveness.

I will stress that the FDA work closely with scientists and the HD community to make clinical trials as efficient and meaningful as possible.

Speed is of the essence for the HD community.

Heartbroken by another loss

As of this writing, Terry is stable, but his prognosis is not positive.

To give me strength as I travel to Maryland on September 21 and take part in the meeting the next day, I will keep fresh my memory of Terry.

I am heartbroken by yet another loss to HD.

As an advocate, I feel I have failed to fulfill the promise of hope presented so often to families such as the Leaches. No 18-year-old should die.

I am comforted to know that Terry is in loving hands – and that he never gave up, always smiling that infectious smile. And I am committed to making sure policymakers know of the people whose lives they could improve and save.

Terry in 2010 as a Hero of the Carlsbad Marathon

Unraveling the mysteries of the mitochondria in Huntington’s disease – and getting fast, clear, and useful results from research studies

In the collaborative quest for Huntington’s disease treatments, deepening affected families’ understanding of the key scientific challenges is vital. It can demystify the process of research, inspire involvement in investigative studies and clinical trials, and ultimately bolster the chances of defeating this horrible malady.

Noting the global nature of HD research, last month I highlighted key work on the West Coast of the United States. Andrew F. Leuchter, M.D., and Michael Levine, Ph.D., plan to measure brain energy waves to decipher the signals emitting from HD-affected individuals. Their work could ultimately lead to new drugs (click here to read more).

On the East Coast, at the Magnetic Resonance Research Center (MRRC) of the Yale School of Medicine, Doug Rothman, Ph.D., and his collaborators will conduct two unique studies that seek to unravel long-standing mysteries about Huntington’s and the mitochondria, the complex powerhouses of most of our cells.

“All the brain cells depend on them very heavily,” Dr. Rothman said during an interview at the MRRC on April 12.

Mitochondria came onto the evolutionary path about a billion years ago, he noted. They use oxygen to burn fuels (such as glucose, or common sugar) to provide energy for brain cells. In focusing on the mitochondria, Dr. Rothman’s studies aim to shed light on the serious energy deficits caused in HD and to provide tools for improving clinical trials.

As the Huntington’s community ramps up to a growing number of those trials, the paramount work of these scientists can help insure clear and useful results.

A mitochondrian (Wikipedia diagram by Mariana Ruiz Villarreal)

Novel and unique human studies

In people carrying the HD genetic abnormality, why do so many brain cells become damaged and eventually die, leading to HD symptoms? For decades, scientists researching this question mainly in animals and cell cultures have found much evidence implicating the mitochondria in the cells’ problems. However, they still don’t know exactly what the problem is.

Using the latest brain-scan technology, Dr. Rothman’s studies will involve human participants. They will focus on the mitochondria and the decline in cellular energy production, one of the main characteristics of HD.

“Anything that impairs the energy supply will severely impact brain function and will eventually impact cellular health,” Dr. Rothman said, adding that researchers suspect that mitochondrial dysfunction plays a part in many other neurological disorders.

Doug Rothman, Ph.D. (photo by Gene Veritas)

The first study seeks to identify a mitochondria-linked biomarker (a sign of disease or a disease mechanism) that could lead to a faster, more efficient way of testing potential HD remedies. The second aims to answer a major question: are less active mitochondria a cause or an effect of the disease?

“There’s lots of preclinical studies that suggest mitochondrial alterations,” Dr. Rothman said, referring to animal studies. “What’s nice is that the MR [magnetic resonance] technology allows this aspect of mitochondrial function to be measured non-invasively in vivo.”

These studies are “novel” and “unique” because they will involve “patients who have the gene,” he added. “Before it would have to be done on a preclinical model. There was no way to directly study humans until the development of the MR technology.”

Described below, the specific types of MR scans in Dr. Rothman’s studies will be used on HD-affected individuals for the first time, he said.

Pioneering the technology

Dr. Rothman helped pioneer this technology. It is recognizable to most people in the form of the MRI scanners that became common in medical diagnostics worldwide over the past two decades.

In working toward his Ph.D. at Yale, received in 1987, Dr. Rothman specialized in a technique known as NMR, nuclear magnetic resonance.  When used in humans NMR is now referred to as MRS, magnetic resonance spectroscopy. He and other specialists have applied MRS to the study of disease. In 1989 he was appointed to the Yale Medical School faculty, and in 1995 he became the director of the Magnetic Resonance Research Center.

As researchers refine these techniques, they have become ever more capable of picking up the resonance – literally a radio frequency – of the chemicals that make up living organisms, including humans.

In both MRS and the more familiar MRI, radio pulses are given to subjects inside huge magnets.  The radio pulses excite (stimulate) chemicals in the body while a person lies in the machine, analogous to a bell being struck. Each compound then resonates (again analogous to a bell) at a characteristic radio frequency. By measuring the radio signal from the different resonating chemicals the chemical composition of different brain regions can be determined.

Dr. Rothman stressed that the technology is safe. “You’re not exposed to any radiation at all – literally just radio frequency,” he said of the scanners, which detect the radio frequencies coming out of the body.

“You literally could set up an FM radio and pick these up,” he continued. “Really, the system’s main difference from a standard radio is just the sensitivity and stability, because we’re talking about very small differences of frequency, as opposed to say a megahertz, as you have in FM radio.”

The scanner sends the readings to a computer for analysis.

Understanding brain metabolism

Using MRS, Dr. Rothman and his colleagues at the MRRC contributed to breakthroughs in understanding the biochemistry of type 2 diabetes. He also helped make important discoveries about the biochemistry of the liver and muscles.

At the same time, he and others discovered ways to measure levels of chemicals in the brain. Those chemicals included metabolites, which provide energy, and neurotransmitters, which are involved in signaling between brain cells.

For the first time in human brain scans, Dr. Rothman and his colleagues detected key chemicals such as ethanol and glucose. They also saw the major neurotransmitters glutamate and GABA (gamma aminobutryric acid), substances mentioned frequently in the world of HD research.

This group of scientists made other important advances in the understanding of brain metabolism. Of particular potential importance for HD, they discovered the energy cost for supporting brain glutamate and GABA neurotransmitter activity, providing a direct link between mitochondrial health and brain function.

As a result of their discoveries, Dr. Rothman and a group of colleagues saw how levels of glutamate and GABA are altered in depression, epilepsy, and other psychiatric disorders, and how drugs can impact those levels.

Dysfunction seen in animals

Several years ago, Dr. Rothman added Huntington’s disease to his focus. Funded by CHDI Foundation, Inc., the multi-million-dollar nonprofit virtual biotech dedicated to finding HD treatments, Dr. Rothman and his lab staff conducted research on mitochondria and brain cell metabolism in two types of transgenic HD mice.

Using MRS scans, in both groups of mice the team found a decline in metabolism in three key regions of the brain (cortex, thalamus, and striatum). They also discovered a reduction in brain cell glutamate and GABA signaling activity.

“The changes were much more profound as the models reached the late premanifest or manifest stage,” Dr. Rothman said during a presentation of the research in February at the CHDI-sponsored 10th Annual HD Therapeutics Conference.

These findings suggested that mitochondrial dysfunction plays a role in HD. This and his upcoming studies are part of a larger group of biomarker studies necessitated by the advent of clinical trials.

You can watch Dr. Rothman’s presentation in the video below.

Evidence for Mitochondrial Dysfunction in Mouse Models of Huntington's Disease? from Gene Veritas on Vimeo.

High-powered brain scans

With CHDI support, Dr. Rothman hopes to carry out the human studies in the second half of this year.

Each study will require about 40 volunteers: 20 early-stage HD-affected individuals and 20 gene-negative volunteers to act as a comparison group. Each study will involve a brain scan and take two or three days, including travel time. The study will cover the cost of travel, food, and lodging. Volunteers can take part in both studies, if they wish.

In the first study participants will undergo a so-called proton scan lasting 60-90 minutes. The Rothman team will use Yale’s 7 Tesla scanner. The number of Teslas corresponds to the power of the magnet, with higher Tesla giving greater sensitivity (the ringing discussed above has a higher amplitude and frequency).

“Seven Tesla is about the highest magnetic field that can be used for human studies,” said Dr. Rothman. “Your molecules move around and jitter and release a radio signal that interferes with the measurement, and so we need as about as high a sensitivity as possible. Interestingly, within a chemical, the protons all have different frequencies. So you can actually identify a chemical based on the pattern of resonance frequencies.”

At this level, the scientists can measure more types of metabolites and with greater sensitivity, allowing them to distinguish between glutamate and another neurotransmitter, glutamine. Both are involved in a cycle involving GABA, brain cell signaling, and metabolism. The research team aims to determine whether glutamine or glutamate is most altered by the disease.

Yale's 7 Tesla scanner (photo by Gene Veritas)

Optimizing treatments

The researchers will focus primarily on glutamine, because it is the most sensitive chemical marker in the brain, but it’s not easily measured in humans at 3 Tesla or lower (scanners with less sensitivity), Dr. Rothman explained.

The more sensitive the biomarker, the better the chance of measuring the effects of the disease and potential treatments, he added.

This biological fine-tuning raises the possibility of studying the disease and testing therapies in small groups, perhaps even single subjects – a far more efficient, inexpensive, and faster way to treatments than the traditional, larger studies involving dozens or scores of individuals.

“The hope is that it would be possible to get immediate feedback before any behavioral-motor changes and use that to optimize individual subjects’ therapy,” Dr. Rothman elaborated.

Tracing the journey of sugar

In the second study Dr. Rothman will use ¹³C (carbon-13) MRS, the same technique used in the HD-mouse mitochondria project (discussed above) and in human scans for a variety of conditions. Carbon-13 is a natural, stable isotope that makes up about 1.1 percent of all the carbon on earth. Researchers use it to label substances so they can be tracked through the body.

Participants will lie in a 4 Tesla scanner for about two hours. They will be continuously injected with ¹³C-labeled glucose through a catheter in one arm. From a catheter in the other arm small blood samples will be taken to read levels of ¹³C and glucose. Glucose is used because it is the main fuel that the mitochondria burn to provide the brain with energy.

Lab assistants will monitor participants’ glucose levels to make sure they remain stable. Afterwards, the participants will receive orange juice and lunch in a standard recovery room, where assistants will make sure that their glucose levels have returned to normal.

As Dr. Rothman explained, the ¹³C MRS technique will allow his team to watch the glucose go through the various stages of the energy cycle in the brain. This metabolic process includes the transformation of glucose into lactate, then into glutamate by way of what is known as the TCA (tricarboxylic acid) cycle in mitochondria. The rate of flow of glucose into the mitochondria is proportional to the amount of energy the mitochondria produce.

“We can also measure the flow from glutamate to glutamine, which gives us the rate of glutamate neurotransmission, a direct measure of brain function,” he added.

As a result, the team can measure the rate of energy production in individual brain cells, as well as the rate of brain signaling (neurotransmission).

Dr. Rothman summarized: “We have a measure of both the energetics of the neuron – how much energy is the mitochondria making – and a measure of the function of the neuron – how much it’s signaling, how much glutamate it’s releasing through the flow into glutamine.”

The team will attempt to answer two questions: whether energy production decreases in early-stage HD individuals, and, if so, whether the drop results from impairments in the mitochondria.

Based on animal studies and previous human studies using other techniques, Dr. Rothman and his team believe they will find diminished energy production in the mitochondria.

“But that doesn’t, by itself, tell us that the mitochondria are causing it,” he said. “It could be many other things.”

Dr. Rothman making an adjustment on Yale's 4 Tesla scanner (above) and standing the in recovery room where ¹³C study volunteers will have glucose readings monitored afterwards (below) (photos by Gene Veritas)

Verifying the impairment

The ¹³C experiment will examine the rate of energy production of the mitochondria. To further tease out the questions about the role of the mitochondria in HD, Dr. Rothman and his team want to measure the demand on the mitochondria for energy production. 

To do so, they will run a second experiment during the ¹³C scans. Using phosphorous magnetic resonance spectroscopy, they will analyze the level of other compounds used for brain cell energy. Specifically, they will measure the synthesis of ATP (adenosine triphosphate) from ADP (adenosine diphosphate) (click here to learn about this process). The breakdown of ATP back into ADP by the mitochondria releases energy to fuel cellular processes, he said.

“In the muscle it fuels contraction,” Dr. Rothman said. “In the brain it fuels neurotransmission. If the mitochondria have a defect or have a low number or activity, they have to be driven harder for the same amount of energy production.”

For this measurement to occur, the participants must have their brains stimulated. “So both people with HD and control subjects will be given visual scenes in the magnet that will force the visual cortex we’re measuring to be active,” Dr. Rothman explained.

If the HD subjects have a mitochondrial impairment, the team will be able to determine whether the mitochondria “are being forced to work harder, because their capacity is less,” he said.

In combination with the ¹³C MRS readings, this experiment will help the scientists conclude whether “the problem is at the mitochondria,” Dr. Rothman said. This knowledge will help in the design of potential remedies and the clinical trials to test them.

The ¹³C study will measure energetics and signaling, as shown in this rendition of the glutamatergic synapse (image courtesy of Dr. Rothman)

Gratitude for the scientists’ work

Dr. Rothman said he expects the proton study to take about 18 months and the ¹³C study about 24 months. Once the studies commence, a call for volunteers will go out from the MRRC. If recruitment goes well, the studies may finish sooner, he said.

Upon the completion of the proton study, CHDI will evaluate the feasibility of glutamine as a treatment biomarker in comparison with glutamate and other MRS biomarkers under study, he added. Later Dr. Rothman’s team will file a report on the studies with CHDI, and they aim to submit their work to a scientific journal.

The engagement of Dr. Rothman and Yale Medical School in HD science exemplifies the seriousness of CHDI and HD researchers in the quest for treatments.

With the goal of unraveling the mysteries of the mitochondria, Dr. Rothman’s experiments can potentially complete key parts of the HD treatment puzzle. The search for effective biomarkers and increased knowledge about the role of the mitochondria can speed the movement of discoveries from scientific bench to patient’s bedside.

As a Yale graduate and carrier of the HD genetic defect, I was especially thrilled to interview Dr. Rothman. My alma mater may very well be helping to save me and thousands of others from the ravages of HD.

I am grateful each day for the commitment of Dr. Rothman and scientists around the globe to defeat HD.

Gene Veritas (aka Kenneth P. Serbin) at Yale University in New Haven, CT, April 2015 (photo by Gene Veritas)

Hope, cutting-edge science, and poignant moments at the World Congress on Huntington’s Disease

The first such HD meeting held in a developing nation, last month’s World Congress on Huntington’s Disease (WCHD) not only highlighted the need for better understanding of the disease in Latin America. It also revealed the growing global importance of the the quest for both better care everywhere and the development of treatments.

Featuring activities for both researchers and families, the sixth WCHD featured some 20 panels, a poster session, a satellite symposium, joint meetings of the International Huntington Association (IHA) and the Associação Brasil Huntington (ABH), entertaining evening wrap-ups by HDBuzz.net editors Dr. Jeff Carroll and Dr. Ed Wild, and a moving presentation by the France-based HD performance group Dingdingdong.

Like most HD conferences, the WCHD stressed advances in the search for treatments. The four-hour-long closing session included an update on clinical trials, a talk on deep brain stimulation and HD, a presentation on cutting-edge RNA-interference-based (RNAi) therapies, and an overview of the efforts to reduce or block the deleterious effects of the faulty protein huntingtin in the brain.

“There is a lot of hope,” said Dr. Doug Macdonald, the director of drug discovery and development for CHDI Management, Inc., which directs the multi-million-dollar effort to defeat HD by the CHDI Foundation, Inc., in his presentation. “There is a rich pipeline of these therapeutics advancing into the clinic. We have direct delivery of huntingtin-lowering agents, the viral delivery of RNAi agents, and viral delivery of zinc finger protein agents.”

Dr. Macdonald provided a clinical-trial timeline for these potential drugs. The first is likely to be the huntingtin-lowering drug under development at Isis Pharmaceuticals, Inc., and Roche, scheduled to enter a Phase I trial by the end of 2014. Other projects may begin trials in the next few years, Dr. Macdonald added.

For a detailed explanation of these approaches and more on timelines, watch Dr. Macdonald’s talk in its entirety in the video below. See also a discussion of other types of trials and general coverage of the WCHD at www.HDBuzz.net.

You can view 32 more chronologically ordered conference-related videos by visiting my 2013 World Congress on Huntington’s Disease album on Vimeo.

Modulating Huntingtin Levels to Treat Huntington's Disease: A Talk by Dr. Doug Macdonald from Gene Veritas on Vimeo.

From exciting science to social consequences

The WCHD scientific presenters focused on a panoply of other HD themes, from exciting developments in basic science to current medical treatments of symptoms to the social consequences of HD.

Dr. Elena Cattaneo of Italy presented the latest research on the origins of the huntingtin gene.

“The normal gene is a gene that everyone has,” Dr. Cattaneo explained. “Everyone in the world has that gene. At some point, we started to think that, if we have that gene, it means that gene is important. So about ten years ago my group, but also other groups, started looking for the function of the normal gene. Of course, we know that in the disease the mutant gene causes the loss of the neurons. But in order to understand more about the mutant version, we wanted to understand what the normal version was doing.”

Scientists discovered that the normal gene is important for “keeping the neurons healthy and alive and working properly,” she said.

The huntingtin gene was “born” in an ameba species 800 million years ago, she continued. “This is the first pluricellular organ, and the huntingtin gene is there. Pluricellular means that cells talk to each other to form an organism…. I started thinking of huntingtin as a gene with a social function, because it brings cells together. So let’s assume that huntingtin is such a gene. Huntingtin is a good gene. It is not a bad gene.”

You can watch Dr. Cattaneo’s fascinating presentation in the video below.

The Role of the Huntingtin Gene in Huntington's Disease: A Presentation by Dr. Elena Cattaneo from Gene Veritas on Vimeo.

Other notable presentations included Portuguese Dr. Joaquim Ferreira’s detailed review of the various ways in which doctors treat patients and Dr. Anita Goh’s discussion of genetic discrimination and HD.

The Latin American perspective

The WCHD brought a key South American perspective on HD.

“For one thing, the participation of a number of Latin American neurologists, geneticists, and family members offered some new views of Huntington's disease in countries such as Brazil, Peru, Argentina, and Colombia – countries we often do not hear about at international HD meetings,” Dr. Alice Wexler, a historian of HD science, observed in an e-mail after the congress. “Because the extent of Huntington's in these countries is not well known, many of these researchers presented epidemiological and demographic information that was new to most HD researchers, along with clinical and genetic data.”

Dr. Robert Weiser of Venezuela provided a view of HD in Maracaibo, Venezuela, the world’s largest known concentration of HD patients, while Dr. Carlos Cosentino of Peru and Dr. Laura Jardim of Brazil presented their unique research on other aspects of HD in the region.

The WCHD highlighted a stark contrast between the First World, where many HD patients can consult with physicians in modern clinics, and Latin America, where large pockets of HD-affected individuals get no medical attention and lack even such basics as clean drinking water.

Several participants noted that such conditions must improve dramatically for these families to take part in the studies and clinical trials crucial for finding treatments, including Enroll-HD, discussed below.

Rodrigo Osorio of Chile and Alice Wexler’s sister Dr. Nancy Wexler of the U.S. gave moving testimony regarding some of the efforts in the region to improve the conditions for patients, while Dr. Ignacio Muñoz-Sanjuan of CHDI advocated for a recently launched charitable, medical, and care initiative serving Latin America called Factor H: Hope, Huntington’s, Humanity. In their interview with me in Spanish, activists Aleska González and Vivian Puchi elaborated on the major challenges facing the HD community in their native Venezuela.

You can watch Muñoz-Sanjuan describe Factor H in the video below.


Factor H: Hope, Huntington's, Humanity from Gene Veritas on Vimeo.

Riveting stories

The WCHD also gave voice to the riveting stories of HD patients, tested and untested at-risk individuals, caregivers, and family members.

I participated in a plenary session titled “Coping.” The session began with a troubling presentation by Dutch Ph.D. student Marlous Hubers on the topic of “suicidality in Huntington’s disease.”

“In general, suicide occurs two to eight times more often in Huntington’s disease than in the general population,” Hubers stated. “In general, it’s said that 5.7 percent of all deaths in HD are due to suicide, which makes it the third or fourth cause of death in HD…. Screening for suicidal ideation is most important in patients with a depressed mood, as all studies found it as an important predictor.”

Shaken by Hubers’ incisive data, I started my own presentation on coping, which followed hers, by observing that “Marlous’s extremely important research really brings home some issues for me. It brings up lots of memories of how I’ve been trying to cope with living gene-positive for Huntington’s disease. I think she hit the nail right on the head with respect to how gene carriers need help, and gene carriers are kind of on their own, not only with respect to suicide, but other aspects of the disease.”

Collecting myself, I proceeded with a detailed rundown of the many strategies I have adopted to avoid the onset of symptoms.

You can watch my presentation in its entirety in the video below.

Coping with the Threat of Huntington's Disease: Gene Veritas speaks at the World Congress on HD from Gene Veritas on Vimeo.

In one of the most poignant moments of the WCHD, Dr. Carroll and his wife Megan revealed how they conceived their HD-free twins, a boy and a girl, using PGD, preimplantation genetic diagnosis.

The topic was particularly striking for Latin Americans. Genetic testing and genetic counseling are still a rarity, and it’s unclear how much people know about PGD or have used it. In addition, abortion is illegal throughout most of the region, and, at least in the Brazilian case, legislation against genetic discrimination is lacking.

Watch the Carrolls discuss PGD and hear the audience discussion in the video below.

Preimplantation Embryo Selection: Avoiding the Transmission of Huntington's Disease from Gene Veritas on Vimeo.

From young people, with love

The WCHD also had a strong youth presence. I interviewed England-based Matty Ellison, the 25-year-old founder of the Huntington’s Disease Youth Organization, about his father’s fight against HD, his own experience of testing positive for the gene at the age of 19, and his international advocacy.

The most unusual and beautiful moment of the WCHD came with the performance of Dingdingdong, a group of young adult performers representing French HD families and reflecting many themes relevant to young people facing HD.

The group put on From Huntingtonland with Love, a three-part presentation in English involving a short play, a video, and a silent dance performance by chogeographer and dancer Anne Collod, in which she mimics the chorea, or involuntary, dance-like movements, suffered by most HD patients.

You can watch Collod in the video below.


A Portrait in Motion of D., a Man Suffering from Huntington's Disease from Gene Veritas on Vimeo.

A costly event

For me, one drawback of the WCHD was the high cost of the venue, the Sheraton Rio Hotel and Resort, a luxury-class facility on the beach of Leblon, one of the world’s most expensive neighborhoods. My room cost nearly $400 per night, the most expensive room I have ever paid for, and out of reach for vast numbers of Latin American families. (And I couldn’t even share that expensive room with my wife, since she was back home with our daughter.)

Along with several family advocates and others, I noted how the exclusive facility, as well as the scheduling of the event the same week as the Rock in Rio music festival, had made it extremely difficult for low and even middle-income families – and perhaps also local research students – to take part.

As an experienced Brazil hand, I thought the organizers might have chosen less expensive, more accessible facilities. In my opinion, holding the meeting in less-glamorous but more convenient São Paulo – where ABH headquarters are located – would have been a good option.

Dozens of Brazilians attended the WCHD, but only a handful of people came from other countries, even from the aforementioned world leader in HD patients, Venezuela.

Nevertheless, as I wrote in my previous article, overall I thought the WCHD ran very smoothly, and families and IHA made important new connections.

A boost to Enroll-HD

Following the WCHD, CHDI ran a seminar to train medical professionals from Argentina, Brazil, Colombia, and Venezuela how to evaluate HD patients and collect medical information on them for Enroll-HD, the recently inaugurated global HD observational study and database.

Enroll-HD aims to improve tools to assess the disease, identify and characterize biomarkers (signs of the disease) necessary for measuring the effectiveness of treatments, recruit participants for other studies and trials, and improve clinical care everywhere.

Featuring Enroll-HD on one of its panels, the WCHD in Rio provided an important moment for publicizing the program and attracting participants.

(I will report on Enroll-HD at the WCHD in a future article.)

Continuing to foster international connections – and greater family participation in future conferences at all levels – will increase the chances of success of Enroll-HD and ultimately the defeat of HD.